Organ System
Organ System
Mechanism
RTK|GPCR|LigG|Nuclear/IC R
RTK
EGF|NGF|PDGF|CSF|FGF|VEGF
EC|L-binding|IC|Tyr kinase activity
2|transmem|Tyr kinase domain
2|hormone-binding site
2xL|full activation|phos IRS-1
SH2|Ras|Raf|Mek|Erk|Elk|c-Myc
PI3K|GLUT4|mem|Glc|Glg
Insulin R
CML
BM malignancy|Phili|9:22|Abl:Bcr
Abl-Bcr fusion|reg Tyr K|Gleevec
Gleevec|Abl-Bcr|Tyr K
B-raf
GPCR
CA|NT|pepH
2nd msgr|cAMP|DAG|PI3|Ca|cGMP
cAMP|PKA (R2C2)|Pl'ase||P'ase|PDE
S
1
Gq
PS
M1
Gq
D
D1
Gi
M2
Gi
D2
1
2
Gs
Gs
M3
Gq
1|1|V1|M1|M3
Gs
H
H1
Gi
H2
Gq
Vp
V1
Gq
Gs
V2
Gs
Gq|PLC|PIP2|DAG|PKC
IP3|Ca|Sm m
1|2|D1|H2|V2
Gs|AC|cAMP|PKA|Ca
M2|2|D2
Gi|AC|cAMP|PKA|MLCK
Ca-CaM
MLCK|NOS|
MLCK
Phos myosin|muscle contraction|
ACh sm m contraction
NOS
NO|relax vasc sm m|vasoD
ACh@vac endothelium
Adr
E|NE
Cholinergic
Ach
PDE5
corpora cavernosa
PDE3
heart
Viagra
affect PDE5 more
U|Br|Bn
U|Br|Bn
Uterus
Breast
Bone
High Co|Low Co
Low Co|High Co
High Co|Low Co
U=endometrial CA
Br=breast CA
Bn=osteoporosis
***Some Rx can be agonist or antagonist depending on
the tissue they are in***
Different Rx effects depends on which Co-reg is
expressed more in the tissue. Some Rx have
preference for one or the other Co-reg (ie. Rolaxifen)
while others go with the flow and exhibit the effects
of the more expressed Co-reg (ie. Tamoxifen).
Faslodex (ICI) is a global antagonist meaning that it
always recruit Co regardless of the [] in the tissue
Estradiol (E2) is a global agonist meaning that it
always recruit Co regardless of the [] in the tissue
Tamoxifen has no preference for Co or Co; dep
solely on which Co-reg is higher
Raloxifen prefers Counless [] diff is too great to
ignore
Tamoxifen
Clomiphene
Raloxifene
Br|Anta|Bn|Antg|U|Agonist
HTh|Antg|Br|NOT Antg
Bn|Antg|U|Antg|Br|Antg
Orphan R
burns fat|liver|muscle|FA|fibrate Rx
FA|ArachA|TZD|Ins sensitiation
up fat storage|mntn Ins sensitivity
ubiquitous expr|low amt|sim to
FXR
CAR
SXR